Joannides R, Haefeli W E, Linder L, Richard V, Bakkali E H, Thuillez C, Lüscher T F
Department of Pharmacology, Rouen University Medical School, France.
Circulation. 1995 Mar 1;91(5):1314-9. doi: 10.1161/01.cir.91.5.1314.
Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans.
Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24 +/- 1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24 +/- 3 to 73 +/- 11 mL/min; P < .01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67 +/- 0.10 to 2.77 +/- 0.12 mm; P < .01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24 +/- 3 to 13 +/- 3 mL/min; P < .05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76 +/- 12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62 +/- 0.11 to 2.55 +/- 0.11 mm; P < .01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery.
The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.
实验证据表明，传导动脉的流量依赖性扩张由一氧化氮（NO）和/或前列环素介导。本研究旨在评估NO或前列环素是否也有助于人类传导动脉的流量依赖性扩张。
使用与多普勒装置耦合的经皮A型回声跟踪系统连续测量16名健康志愿者（年龄24±1岁）的桡动脉内径（ID），以测量桡动脉血流。在8名受试者中，将导管插入肱动脉以测量动脉压并注入一氧化氮合酶抑制剂NG-单甲基-L-精氨酸（L-NMMA；8μmol/min，持续7分钟；注入速率0.8 mL/min）。在注入L-NMMA或阿司匹林之前和之后，评估流量依赖性扩张，作为桡动脉对流量急性增加（3分钟袖带腕部阻断后的反应性充血）的反应。在对照条件下，阻断解除导致桡动脉血流显著增加（从24±3增至73±11 mL/min；P<.01），随后桡动脉直径延迟增加（流量介导的扩张；从2.67±0.10增至2.77±0.12 mm；P<.01），心率或动脉压无任何变化。L-NMMA降低了基础前臂血流（从24±3降至13±3 mL/min；P<.05），但不影响基础桡动脉直径、心率或动脉压，而阿司匹林（口服1 g）无任何血流动力学效应。在存在L-NMMA的情况下，充血期间的峰值血流反应未受影响（76±12 mL/min），但充血反应的持续时间显著缩短，桡动脉的流量依赖性扩张被消除并转变为血管收缩（从2.62±0.11降至2.55±0.11 mm；P<.01）。相比之下，阿司匹林不影响充血反应或桡动脉的流量依赖性扩张。
本研究表明，NO而非前列环素对于人类大动脉的流量介导扩张至关重要。因此，在临床研究中，这种反应可作为检测L-精氨酸/NO途径的一项测试。
